CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells

T. G. Moreira, L. S. Horta, A. C. Gomes-Santos, R. P. Oliveira, N. M.G.P. Queiroz, D. Mangani, B. Daniel, A. T. Vieira, S. Liu, A. M. Rodrigues, D. A. Gomes, G. Gabriely, E. Ferreira, H. L. Weiner, R. M. Rezende, Laszlo Nagy, A. M.C. Faria

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Abstract

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-β via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-β)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - Jan 1 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Moreira, T. G., Horta, L. S., Gomes-Santos, A. C., Oliveira, R. P., Queiroz, N. M. G. P., Mangani, D., Daniel, B., Vieira, A. T., Liu, S., Rodrigues, A. M., Gomes, D. A., Gabriely, G., Ferreira, E., Weiner, H. L., Rezende, R. M., Nagy, L., & Faria, A. M. C. (Accepted/In press). CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells. Mucosal Immunology. https://doi.org/10.1038/s41385-018-0090-8